P577: EFFICACY OF SELINEXOR COMBINED WITH A HYPOMETHYLATING AGENT IN THE TREATMENT OF REFRACTORY/RELAPSED ACUTE MYELOID LEUKEMIA IN PATIENTS EXPOSED TO VENETOCLAX
Authors: Jian Zhang, Baoquan Song, Xin Kong, Yin Liu, Hanlin Yang, Huiying Qiu, Depei Wu
Journal: HemaSphere (2023)

Background: Finding new therapeutic approaches for patients with refractory/relapsed (R/R) AML with poor therapeutic effects in response to traditional chemotherapy and targeted apoptosis pathway remains urgently needed. Previous studies have shown that selinexor as a selective inhibitor of XPO1 is emerging as a potentially effcacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. Aims: To investigate efficacy and safety of selinexor combined with a hypomethylating agent (HMA) in R/R AML. Methods: We conducted a monocentric retrospective analysis on adult patients unsuitable for intensive therapy (unfit) R/R AML, who started selinexor combination regimens between May 2021 and December 2022. AML genetic risk stratification and response criteria were assessed in accordance with the 2022 European Leukemia Net (ELN) consensus. The selinexor + HMA plan is as follows: selinexor 40 mg BIW × 3 weeks orally; DAC 10 mg·day−1 for 7–10 days intravenously or azacytidine (AZA) 75 mg·m−2·day−1 subcutaneously on day 1–day 7 (for patients over 60 years of age, the dose was halved). Allo-SCT was performed on suitable patients. Results: A total of 12 patients with R/R AML treated with selinexor-based combinations were enrolled in this study, including 7 patients with refractory AML and 5 patients with relapsed AML (including 1 with post-transplant recurrence). The median age of the patients was 36 years (18–68 years). All patients showed intermediate or adverse ELN genetic risk. All patients had previously received venetoclax-based combinations, and 58% (7/12) had been treated with HMAs. The baseline information of the patients is shown in Table 1. The overall response rate (ORR) was 66.7% (8/12) with a combined CR rate (CRc) of 50% (6/12). Among the 6 patients with CRc, 3 (50%) had negative minimal residual disease (MRD) (≤1*10−3). CRc remained at 42.9% (3/7) who previously exposed to HMAs-based therapy but reached 100% without exposure history. 12 patients with R/R AML were followed for a median of 8.2 months. The median OS was 5 months, and the median DFS was 4.5 months. 66.7% (8/12) of the patients had received transplants, and 50% (6/12) of the patients survived without loss to follow-up. Among the 6 patients with complex chromosome karyotypes, 3 attained CR. In addition, patient with poor prognosis mutated or fusion genes, such as TP53, FLT3-ITD, MLL-AF6, TLS-ERG, and AML1-ETO, could still obtain CR from this regimen. Remission was achieved in patients with secondary AML (MDS transformation and complicated with myelofibrosis). The above is worthy of further attention (Figure 1). Most common grade 3 or 4 adverse events were neutropenia (83.3%), thrombocytopenia (58%) and the median time for recovery respectively was 14 (8–21) and 16 (8–24) days. Common non-hematologic toxicitys were infection (66.7%) and gastrointestinal reactions (66.7%). Summary/Conclusion: The results of this real world monocentric study confirmed that the association of selinexor and HMAs is a viable and safe option for patients with unfit R/R AML, especially who without exposed to HMAs may benefited more from this therapeutic regimen. Studies have shown that selective inhibition of nuclear export (SINE) can also be potentially used against COVID-19 due to its effective inhibition of viral proliferation and proinflammatory cytokine release. This possibility can be further explored this therapeutic regimen in patients complicated with COVID-19 infection.Keywords: relapsed/refractory, AML